Jun 19, 2008

Molecular Imaging Sheds New Light On Progression Of Alzheimer's Disease

The groundbreaking discovery by University of Pittsburgh researchers Chester Mathis, PhD, and William Klunk, MD, PhD, is being watched with great interest.

Pittsburgh Compound B (PIB) binds to the abnormal amyloid plaque in the brain. When imaged with a PET scan, PIB shows researchers actual pathological changes in the brain that could turn out to be the best and earliest signs of the disease.

Researchers at the University of Pittsburgh Medical Center (UPMC) are revolutionizing the fight against Alzheimer’s disease (AD). Scientists and researchers at the University of Pittsburgh recently discovered a new agent, dubbed “Pittsburgh Compound B,” which allows researchers to visualize for the first time in living people the brain plaque suspected of causing the memory-stealing disease. Previously, the presence of plaque could be confirmed only during autopsy.

Pittsburgh Compound B (PIB) binds to the abnormal amyloid plaque in the brain. When imaged with a PET scan, PIB shows researchers actual pathological changes in the brain that could turn out to be the best and earliest signs of the disease. It may be possible that these changes could be detected as many as 10 years before patients experience serious memory loss.

The groundbreaking discovery by University of Pittsburgh researchers Chester Mathis, PhD, and William Klunk, MD, PhD, is being watched with great interest. Along with Drs. Klunk and Mathis, researchers like Steven DeKosky, MD, director of the Alzheimer Disease Research Center at UPMC, are currently collaborating with investigators around the world to further study PIB and other compounds, as well as potential new treatments for Alzheimer’s.

Pittsburgh Compound B was developed after more than a decade of work by University Drs. Klunk and Mathis. Dr. Klunk is an associate professor of psychiatry who studies Alzheimer’s disease, while Dr. Mathis specializes in developing radiopharmaceuticals — compounds that are injected into the body and temporarily emit radioactive particles that can be captured by PET imaging to reveal anatomical clues.

Working with three classes of dyes used to detect plaque in the lab, Drs. Klunk and Mathis worked for years testing hundreds of compounds before developing PIB.

“This is in the early stages of development,” says Dr. DeKosky. “But if our success continues, it’s possible there could be a commercially available product for the early diagnosis of Alzheimer’s within the next decade.”

Using PIB, doctors may someday be able to follow the progression of the disease and identify people who are at increased risk for AD long before any symptoms occur.

“Until the development of Pittsburgh Compound B, there was no way to measure a decrease in AD plaque or possible remission of the disease,” says Dr. DeKosky. “What makes PIB remarkable is that, for the first time, doctors may be able to tell definitively if treatment is working.” Dr. DeKosky says before this discovery by Drs. Mathis and Klunk, no one was able to develop a tracer that binds to the specific abnormal protein in AD. All of the other imaging studies simply show shrinkage in parts of the brain or brain activity changes in different regions.

“For the last 20 years, we’ve talked about finding a noninvasive way to make a definite and specific diagnosis and being able to quantify the amount of plaque in the brains of people who have AD,” says Dr. DeKosky. “If we can make a specific diagnosis through imaging, then we can track the effectiveness of new drugs and other treatments. There is nothing out there right now anywhere near as direct, that can tell us definitively whether or not a drug reaction and response helps the disease.”

Furthermore, use of the compound may also tell researchers whether the hypotheses upon which therapies are being developed are correct. “That’s important, as is identifying early-stage patients before it’s too late,” says Dr. DeKosky.

“The future is very exciting, and it’s satisfying to know that we were at the forefront of advancing the science,” says Dr. Mathis. “Right now we’re setting the stage to use Pittsburgh Compound B in collaboration with a number of companies that are trying to target therapies for AD. If these therapies do what we hope they will do, then it will become more important to determine if a person has AD at an earlier stage.”

Dr. Mathis says another very important goal will be to nail down amyloid plaque’s exact role in Alzheimer’s disease. While most doctors suspect that it causes Alzheimer’s, there isn’t yet 100 percent agreement on the theory. If amyloid plaque turns out not to be a central cause, Dr. Mathis says, such a finding could completely redirect research.

Finally, PIB and improved radiotracers now under development at the University of Pittsburgh will allow researchers to follow amyloid deposits in Alzheimer’s patients and older people without the disease, helping to better define the normal aging process in the brain.

Alzheimer’s is a very complex disease, one that is just beginning to be understood. It steals the mind and memory. It devastates families and makes strangers out of life-long partners. Approximately 4 million Americans have Alzheimer’s, and if left unchecked, it will strike as many as 14 million during the next 50 years. UPMC’s new research may stem the advance of this debilitating disease.

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